This research project contains several specific subprojects related to genetic and metabolic disorders: (a) Oxalate metabolism. This laboratory has continued as a reference center for the diagnosis and classification of patients with various forms of disorders associated with excessive urinary excretion of oxalate resulting in calcium oxalate stone diathesis. A series of potential inhibitors of oxalate synthesis has been developed and shown to be effective in vitro. They are now being evaluated in vivo. (b) Collagen metabolism. Osteogenesis imperfecta is a rare but serious disorder of connective tissue synthesis. Tissue culture of fibroblasts from patients with osteogenesis imperfecta is being undertaken to study and characterize the collagen and procollagen being synthesized - both its rate of synthesis and possible abnormalities in structure. (c) Schizophrenia. Ingestion of large amounts of methionine may exacerbate schizophrenia, an observation confirmed repeatedly over the past 12 years. This has usually been attributed to the presence of excessive methyl groups. Studies are being undertaken with schizophrenic patients to see if the abnormalities may be in the metabolism of the homocysteine residue of the molecule rather than in the methyl group.